Efficacy and Safety of Sarilumab in patients with COVID19 Pneumonia: A Randomized, Phase III Clinical Trial (SARTRE Study)
Aránzazu Sancho‐López, Antonio F Caballero-Bermejo, Belén Ruíz‐Antorán, Elena Múñez, Mercedes García Gasalla, Juan Manuel Buades, Marta González Rozas, María López Veloso, Ana Muñoz Gómez, Ana Cuenca Abarca, Pedro Durán del Campo, Fátima Ibáñez, Alberto Díaz de Santiago, Yolanda Romero, Jorge Calderón‐Parra, Ilduara Pintos, Adrián Ferré Beltrán, Gustavo Adolfo Centeno-Soto, J. García Campos, António Ramos, C. Avendaño, Ana Fernández‐Cruz, the SARTRE-Study Group, Aránzazu Sancho‐López, Antonio F. Bermejo Caballero, Belén Ruiz-Antorán, Ana Fernández‐Cruz, Elena Múñez, Antonio Ramos Martínez, Cristina Avendaño-Solá, Elena Diago-Sempere, Pedro Durán del Campo, Fátima Ibáñez, Alberto Díaz de Santiago, Yolanda Romero, Jorge Calderón Parra, Ilduara Pinto, Gustavo Centeno, Concepción Payares, Almudena Ramírez‐García, Laura Javaloyes, María de la Encina Higuera, Rocío Layunta Acero, Laura Vicente-Vicente, Paloma Rodríguez Araque, Piedad Ussetti, Rosa Malo de Molina, Andrea Trisán Alonso, M. Valle, Fernando Corella, María Luisa JiménezJiménez, Laura Zapata Ferrer, Jorge Ramos, Alejandro Junco-Vicente, José Campos, Alejandro Callejas Díaz, Sara de la Fuente Moral, Pedro Laguna, Gema Vázquez Contreras, Alejandro Muñoz Serrano, Isolina Baños Pérez, Víctor Moreno Torres-Concha, Alfonso Ángel-Moreno Maroto, Esther Montero Hernández, Ma Carmen Máinez Saíz, Ma Cruz Carreño Hernández, Rosa Muñoz de Benito, Susana Mellor Pita, Pablo Tutor de Ureta, Miriam Aguilar Pérez, Gema Díaz Nuevo, Christian García Fadul, B. Jara Chinarro, Rosalía Laporta Hernández, María Lázaro de la FuenteCarrasco, Cristina Gallo, Patricia Mínguez Clemente, R. Arca, Marta Erro IribarrenIribarren, Ane Andrés Eisenhofer, Itziar Diego Yagüe, Ignacio Donate VelascoVelasco, Gabriela Escudero López, Esther Expósito Palomo, Amy Galán Gómez, Sonia García, Javier Gómez Irusta, Edith Vanessa Gutiérrez Abreu, Isabel Gutiérrez, Ángela Gutiérrez Rojas, Andrea Gutiérrez Villanueva, Jesús Herráiz Jiménez, María Martínez Urbistondo, Fernando Martínez Vara, Patricia Mills Sánchez, Alberto Mora Vargas, Ignacio Morrás De La Torre, Enrique Sánchez Chica, Ángela Valencia Alijo, Jos Manuel Vázquez Comendador
Abstract
INTRODUCTION: SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS). METHODS: We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15. RESULTS: A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48-2.20). No relevant safety issues were identified. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.